Psychedelics as a treatment for patients with post-traumatic stress disorder (PTSD)
DOI:
https://doi.org/10.12775/JEHS.2024.63.004Keywords
PTSD, trauma, psychedelics, MDMA, treatmentAbstract
Introduction and purpose: Post-traumatic stress disorder is a psychiatric condition following an extreme event that causes a near death of an involved individual. Since conventional treatments using selective serotonin reuptake inhibitors do not consistently yield therapeutic success, alternative substances are being explored as potential solutions. This study aims to compile information regarding the outcomes of utilizing psychedelics in individuals diagnosed with PTSD.
Brief description of the state of knowledge: In July 2023, after a number of clinical trials and 20-year-long efforts to overturn the impact of a prohibition, Australia became the first country to allow doctors, in clinical development and under strict control, to use the 3,4-methylenedioxymethamphetamine (MDMA) commonly known as ecstasy, as well as psylocybin in patients with post-traumatic stress disorder or depression [8]. There is a noticeable annual growth of inquiries on PubMed involving the keywords "psychedelics" and "therapeutic", amounting to 92 in 2000 and topped by 738 searches in 2023, whereas the total number of results consists of 8415 positions. Therapeutic effects of psychedelics are becoming more recognized over time.
Summary: Post-Traumatic Stress Disorder (PTSD) is a complex condition that affects both the psychological and somatic aspects of the body. Thus, a multidimensional intervention is indicated. The use of psychedelics might contribute to improvements not only in the severity of PTSD but also in depression or pain. Further research on a larger group of participants should be carried out to assess the potential role of psychedelics in conventional medicine in the future, alongside psychotherapy.
References
Latimer D, Stocker MD, Sayers K, Green J, Kaye AM, Abd-Elsayed A, Cornett EM, Kaye AD, Varrassi G, Viswanath O, Urits I. MDMA to Treat PTSD in Adults. Psychopharmacol Bull. 2021 Jun 1;51(3):125-149. PMID: 34421149; PMCID: PMC8374929.
Mitchell JM, Bogenschutz M, Lilienstein A, Harrison C, Kleiman S, Parker-Guilbert K, Ot'alora G M, Garas W, Paleos C, Gorman I, Nicholas C, Mithoefer M, Carlin S, Poulter B, Mithoefer A, Quevedo S, Wells G, Klaire SS, van der Kolk B, Tzarfaty K, Amiaz R, Worthy R, Shannon S, Woolley JD, Marta C, Gelfand Y, Hapke E, Amar S, Wallach Y, Brown R, Hamilton S, Wang JB, Coker A, Matthews R, de Boer A, Yazar-Klosinski B, Emerson A, Doblin R. MDMA-assisted therapy for severe PTSD: a randomized, double-blind, placebo-controlled phase 3 study. Nat Med. 2021 Jun;27(6):1025-1033. doi: 10.1038/s41591-021-01336-3. Epub 2021 May 10. PMID: 33972795; PMCID: PMC8205851.
Williams T, Phillips NJ, Stein DJ, Ipser JC. Pharmacotherapy for post traumatic stress disorder (PTSD). Cochrane Database Syst Rev. 2022 Mar 2;3(3):CD002795. doi: 10.1002/14651858.CD002795.pub3. PMID: 35234292; PMCID: PMC8889888.
Feduccia AA, Mithoefer MC. MDMA-assisted psychotherapy for PTSD: Are memory reconsolidation and fear extinction underlying mechanisms? Prog Neuropsychopharmacol Biol Psychiatry. 2018 Jun 8;84(Pt A):221-228. doi: 10.1016/j.pnpbp.2018.03.003. Epub 2018 Mar 7. PMID: 29524515.
Goodnight JRM, Ragsdale KA, Rauch SAM, Rothbaum BO. Psychotherapy for PTSD: An evidence-based guide to a theranostic approach to treatment. Prog Neuropsychopharmacol Biol Psychiatry. 2019 Jan 10;88:418-426. doi: 10.1016/j.pnpbp.2018.05.006. Epub 2018 May 18. PMID: 29786514.
https://www.sciencedirect.com/science/article/abs/pii/S027858461830143X?via%3Dihub
Choi KR, Seng JS, Briggs EC, Munro-Kramer ML, Graham-Bermann SA, Lee RC, Ford JD. The Dissociative Subtype of Posttraumatic Stress Disorder (PTSD) Among Adolescents: Co-Occurring PTSD, Depersonalization/Derealization, and Other Dissociation Symptoms. J Am Acad Child Adolesc Psychiatry. 2017 Dec;56(12):1062-1072. doi: 10.1016/j.jaac.2017.09.425. Epub 2017 Oct 4. PMID: 29173740; PMCID: PMC5726572.
Maercker A, Cloitre M, Bachem R, Schlumpf YR, Khoury B, Hitchcock C, Bohus M. Complex post-traumatic stress disorder. Lancet. 2022 Jul 2;400(10345):60-72. doi: 10.1016/S0140-6736(22)00821-2. PMID: 35780794.
Haridy R. Australia to prescribe MDMA and psilocybin for PTSD and depression in world first. Nature. 2023 Jul;619(7969):227-228. doi: 10.1038/d41586-023-02093-8. PMID: 37386185.
Oehen Peter, Gasser Peter. Using a MDMA- and LSD-Group Therapy Model in Clinical Practice in Switzerland and Highlighting the Treatment of Trauma-Related Disorders. Frontiers in Psychiatry.13. 2022 https://www.frontiersin.org/articles/10.3389/fpsyt.2022.863552 DOI=10.3389/fpsyt.2022.863552 ISSN=1664-0640
Lowe H, Toyang N, Steele B, Valentine H, Grant J, Ali A, Ngwa W, Gordon L. The Therapeutic Potential of Psilocybin. Molecules. 2021 May 15;26(10):2948. doi: 10.3390/molecules26102948. PMID: 34063505; PMCID: PMC8156539.
Szafoni S, Więckiewicz G, Pudlo R, Gorczyca P, Piegza M. Will MDMA-assisted psychotherapy become a breakthrough in treatment-resistant post-traumatic stress disorder? A critical narrative review. Psychiatr Pol. 2022 Aug 31;56(4):823-836. English, Polish. doi: 10.12740/PP/OnlineFirst/133919. Epub 2022 Aug 31. PMID: 37074831.
Nutt D. Psychedelic drugs-a new era in psychiatry? . Dialogues Clin Neurosci. 2019;21(2):139-147. doi: 10.31887/DCNS.2019.21.2/dnutt. PMID: 31636488; PMCID: PMC6787540.
Maeng, S., Zarate, C., Du, J., Schloesser, R., McCammon, J., Chen, G., & Manji, H. (2008). Cellular Mechanisms Underlying the Antidepressant Effects of Ketamine: Role of α-Amino-3-Hydroxy-5-Methylisoxazole-4-Propionic Acid Receptors. Biological Psychiatry, 63, 349-352. https://doi.org/10.1016/j.biopsych.2007.05.028.
Mihaljević S, Pavlović M, Reiner K, Ćaćić M. Therapeutic Mechanisms of Ketamine. Psychiatr Danub. 2020 Autumn-Winter;32(3-4):325-333. doi: 10.24869/psyd.2020.325. PMID: 33370729.
Zanos P, Gould TD. Mechanisms of ketamine action as an antidepressant. Mol Psychiatry. 2018 Apr;23(4):801-811. doi: 10.1038/mp.2017.255. Epub 2018 Mar 13. PMID: 29532791; PMCID: PMC5999402.
Zanos P, Moaddel R, Morris PJ, Riggs LM, Highland JN, Georgiou P, Pereira EFR, Albuquerque EX, Thomas CJ, Zarate CA Jr, Gould TD. Ketamine and Ketamine Metabolite Pharmacology: Insights into Therapeutic Mechanisms. Pharmacol Rev. 2018 Jul;70(3):621-660. doi: 10.1124/pr.117.015198. Erratum in: Pharmacol Rev. 2018 Oct;70(4):879. PMID: 29945898; PMCID: PMC6020109.
Anil K. Malhotra, Debra A. Pinals, Herbert Weingartner, Karen Sirocco, C. David Missar, David Pickar, Alan Breier, NMDA receptor function and human cognition: The effects of ketamine in healthy volunteers, Neuropsychopharmacology, Volume 14, Issue 5, 1996, Pages 301-307, ISSN 0893-133X, https://doi.org/10.1016/0893-133X(95)00137-3. (https://www.sciencedirect.com/science/article/pii/0893133X95001373)
Figurasin R, Maguire NJ. 3,4-Methylenedioxy-Methamphetamine Toxicity. 2022 Sep 4. In: StatPearls [Internet]. Treasure Island (FL): StatPearls Publishing; 2024 Jan–. PMID: 30860717.
Feduccia AA, Mithoefer MC. MDMA-assisted psychotherapy for PTSD: Are memory reconsolidation and fear extinction underlying mechanisms? Prog Neuropsychopharmacol Biol Psychiatry. 2018 Jun 8;84(Pt A):221-228. doi: 10.1016/j.pnpbp.2018.03.003. Epub 2018 Mar 7. PMID: 29524515.
de la Torre R, Farré M, Roset PN, Pizarro N, Abanades S, Segura M, Segura J, Camí J. Human pharmacology of MDMA: pharmacokinetics, metabolism, and disposition. Ther Drug Monit. 2004 Apr;26(2):137-44. doi: 10.1097/00007691-200404000-00009. PMID: 15228154.
Schenk S, Newcombe D. Methylenedioxymethamphetamine (MDMA) in Psychiatry: Pros, Cons, and Suggestions. J Clin Psychopharmacol. 2018 Dec;38(6):632-638. doi: 10.1097/JCP.0000000000000962. PMID: 30303861.
Geiger HA, Wurst MG, Daniels RN. DARK Classics in Chemical Neuroscience: Psilocybin. ACS Chem Neurosci. 2018 Oct 17;9(10):2438-2447. doi: 10.1021/acschemneuro.8b00186. Epub 2018 Jul 16. PMID: 29956917.
Pearson C, Siegel J, Gold JA. Psilocybin-assisted psychotherapy for depression: Emerging research on a psychedelic compound with a rich history. J Neurol Sci. 2022 Mar 15;434:120096. doi: 10.1016/j.jns.2021.120096. Epub 2021 Dec 16. PMID: 34942586.
Passie T, Seifert J, Schneider U, Emrich HM. The pharmacology of psilocybin. Addict Biol. 2002 Oct;7(4):357-64. doi: 10.1080/1355621021000005937. PMID: 14578010.
Goodwin GM, Aaronson ST, Alvarez O, Arden PC, Baker A, Bennett JC, Bird C, Blom RE, Brennan C, Brusch D, Burke L, Campbell-Coker K, Carhart-Harris R, Cattell J, Daniel A, DeBattista C, Dunlop BW, Eisen K, Feifel D, Forbes M, Haumann HM, Hellerstein DJ, Hoppe AI, Husain MI, Jelen LA, Kamphuis J, Kawasaki J, Kelly JR, Key RE, Kishon R, Knatz Peck S, Knight G, Koolen MHB, Lean M, Licht RW, Maples-Keller JL, Mars J, Marwood L, McElhiney MC, Miller TL, Mirow A, Mistry S, Mletzko-Crowe T, Modlin LN, Nielsen RE, Nielson EM, Offerhaus SR, O'Keane V, Páleníček T, Printz D, Rademaker MC, van Reemst A, Reinholdt F, Repantis D, Rucker J, Rudow S, Ruffell S, Rush AJ, Schoevers RA, Seynaeve M, Shao S, Soares JC, Somers M, Stansfield SC, Sterling D, Strockis A, Tsai J, Visser L, Wahba M, Williams S, Young AH, Ywema P, Zisook S, Malievskaia E. Single-Dose Psilocybin for a Treatment-Resistant Episode of Major Depression. N Engl J Med. 2022 Nov 3;387(18):1637-1648. doi: 10.1056/NEJMoa2206443. PMID: 36322843.
González-Maeso J, Weisstaub NV, Zhou M, Chan P, Ivic L, Ang R, Lira A, Bradley-Moore M, Ge Y, Zhou Q, Sealfon SC, Gingrich JA. Hallucinogens recruit specific cortical 5-HT(2A) receptor-mediated signaling pathways to affect behavior. Neuron. 2007 Feb 1;53(3):439-52. doi: 10.1016/j.neuron.2007.01.008. PMID: 17270739.
Ko K, Kopra EI, Cleare AJ, Rucker JJ. Psychedelic therapy for depressive symptoms: A systematic review and meta-analysis. J Affect Disord. 2023 Feb 1;322:194-204. doi: 10.1016/j.jad.2022.09.168. Epub 2022 Oct 7. Erratum in: J Affect Disord. 2024 Mar 1;348:409. PMID: 36209780.
Abdallah CG, Roache JD, Gueorguieva R, Averill LA, Young-McCaughan S, Shiroma PR, Purohit P, Brundige A, Murff W, Ahn KH, Sherif MA, Baltutis EJ, Ranganathan M, D'Souza D, Martini B, Southwick SM, Petrakis IL, Burson RR, Guthmiller KB, López-Roca AL, Lautenschlager KA, McCallin JP 3rd, Hoch MB, Timchenko A, Souza SE, Bryant CE, Mintz J, Litz BT, Williamson DE, Keane TM, Peterson AL, Krystal JH. Dose-related effects of ketamine for antidepressant-resistant symptoms of posttraumatic stress disorder in veterans and active duty military: a double-blind, randomized, placebo-controlled multi-center clinical trial. Neuropsychopharmacology. 2022 Jul;47(8):1574-1581. doi: 10.1038/s41386-022-01266-9. Epub 2022 Jan 19. Erratum in: Neuropsychopharmacology. 2022 May 11;: PMID: 35046508; PMCID: PMC8767037.
Feder A, Costi S, Rutter SB, Collins AB, Govindarajulu U, Jha MK, Horn SR, Kautz M, Corniquel M, Collins KA, Bevilacqua L, Glasgow AM, Brallier J, Pietrzak RH, Murrough JW, Charney DS. A Randomized Controlled Trial of Repeated Ketamine Administration for Chronic Posttraumatic Stress Disorder. Am J Psychiatry. 2021 Feb 1;178(2):193-202. doi: 10.1176/appi.ajp.2020.20050596. Epub 2021 Jan 5. PMID: 33397139.
Dadabayev AR, Joshi SA, Reda MH, Lake T, Hausman MS, Domino E, Liberzon I. Low Dose Ketamine Infusion for Comorbid Posttraumatic Stress Disorder and Chronic Pain: A Randomized Double-Blind Clinical Trial. Chronic Stress (Thousand Oaks). 2020 Dec 22;4:2470547020981670. doi: 10.1177/2470547020981670. PMID: 33426410; PMCID: PMC7758557.
Mitchell JM, Bogenschutz M, Lilienstein A, Harrison C, Kleiman S, Parker-Guilbert K, Ot'alora G M, Garas W, Paleos C, Gorman I, Nicholas C, Mithoefer M, Carlin S, Poulter B, Mithoefer A, Quevedo S, Wells G, Klaire SS, van der Kolk B, Tzarfaty K, Amiaz R, Worthy R, Shannon S, Woolley JD, Marta C, Gelfand Y, Hapke E, Amar S, Wallach Y, Brown R, Hamilton S, Wang JB, Coker A, Matthews R, de Boer A, Yazar-Klosinski B, Emerson A, Doblin R. MDMA-assisted therapy for severe PTSD: a randomized, double-blind, placebo-controlled phase 3 study. Nat Med. 2021 Jun;27(6):1025-1033. doi: 10.1038/s41591-021-01336-3. Epub 2021 May 10. PMID: 33972795; PMCID: PMC8205851.
Mithoefer MC, Mithoefer AT, Feduccia AA, Jerome L, Wagner M, Wymer J, Holland J, Hamilton S, Yazar-Klosinski B, Emerson A, Doblin R. 3,4-methylenedioxymethamphetamine (MDMA)-assisted psychotherapy for post-traumatic stress disorder in military veterans, firefighters, and police officers: a randomised, double-blind, dose-response, phase 2 clinical trial. Lancet Psychiatry. 2018 Jun;5(6):486-497. doi: 10.1016/S2215-0366(18)30135-4. Epub 2018 May 1. PMID: 29728331.
Oehen P, Traber R, Widmer V, Schnyder U. A randomized, controlled pilot study of MDMA (± 3,4-Methylenedioxymethamphetamine)-assisted psychotherapy for treatment of resistant, chronic Post-Traumatic Stress Disorder (PTSD). J Psychopharmacol. 2013 Jan;27(1):40-52. doi: 10.1177/0269881112464827. Epub 2012 Oct 31. PMID: 23118021.
Irizarry R, Winczura A, Dimassi O, Dhillon N, Minhas A, Larice J. Psilocybin as a Treatment for Psychiatric Illness: A Meta-Analysis. Cureus. 2022 Nov 22;14(11):e31796. doi: 10.7759/cureus.31796. PMID: 36569662; PMCID: PMC9779908.
Downloads
Published
How to Cite
Issue
Section
License
Copyright (c) 2024 Krzysztof Marcinkowski, Agata Mazur, Magdalena Madera, Sylwia Mazur, Karolina Strus, Aleksy Bizan, Emilia Nagórska, Roksana Zdunek, Natalia Dąbrowska, Aleksandra Kublińska
This work is licensed under a Creative Commons Attribution-NonCommercial-ShareAlike 4.0 International License.
The periodical offers access to content in the Open Access system under the Creative Commons Attribution-NonCommercial-ShareAlike 4.0
Stats
Number of views and downloads: 667
Number of citations: 0